scholarly journals Transmitted Drug Resistance in Antiretroviral Therapy-Naive Persons With Acute/Early/Primary HIV Infection: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunxiang Guo ◽  
Yaxin Wu ◽  
Yang Zhang ◽  
Xinchao Liu ◽  
Aixin Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Meta Analysis ◽  
Antiretroviral Drugs ◽  
Cochrane Library ◽  
Transmitted Drug Resistance ◽  
Reverse Transcriptase Inhibitors ◽  
Primary Hiv Infection

Background: The widespread use of antiretroviral therapy (ART) has raised concerns about the emergence of HIV transmitted drug resistance (TDR). Acute HIV infection (AHI) was the most appropriate time to detect the spread of TDR. In this meta-analysis, our purpose was to evaluate the level of TDR in ART-naive patients with primary HIV infection (PHI)/AHI/early HIV infection (EHI) and to describe the critical drug-resistant mutations.Methods: We systematically searched the literature between January 1, 2008, and April 30, 2021, in PubMed, Web of Science, Embase, and the Cochrane Library. To evaluate the overall prevalence of TDR, we extracted raw data and analyzed prevalence estimates using Stata SE.Results: The data of this meta-analysis come from 12 observational studies, covering 3,558 ART-naive individuals with PHI, AHI, or EHI. The overall prevalence of HIV-TDR is 9.3% (95% CI: 6.8%–11.8%, I2 = 81.1%, in 11 studies). The prevalence of resistance by drug class is the highest for the nonnucleoside reverse transcriptase inhibitors (NNRTIs) at 5.7% (95% CI: 2.9%–8.5%, I2 = 96.6%, in 11 studies), followed by nucleoside reverse transcriptase inhibitors (NRTIs) at 3.4% (95% CI: 1.8%–5.0%, I2 = 86.3%, in 10 studies) and protease inhibitors (PIs) at 3.3% (95% CI: 2.7%–3.9%, I2 = 15.6%, in 10 studies). The prevalence of TDR to integrase inhibitors (INIs) is 0.3% (95% CI: 0.1%–0.7%, I2 = 95.9%, in three studies), which is the lowest among all antiretroviral drugs.Conclusion: The overall prevalence of TDR is at a moderate level among AHI patients who have never received ART. This emphasizes the importance of baseline drug resistance testing for public health surveillance and guiding the choice of ART. In addition, the prevalence of TDR to NNRTIs is the highest, while the TDR to INIs is the lowest. This may guide the selection of clinical antiretroviral drugs.

scholarly journals Transmitted drug resistance in ART-naive persons with acute/ early/ primary HIV infection: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Chun-Xiang GUO ◽  
Ya-Xin WU ◽  
Yang ZHANG ◽  
Xin-Chao LIU ◽  
Ai-Xin LI ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Infection ◽  
Meta Analysis ◽  
Antiretroviral Drugs ◽  
Cochrane Library ◽  
Resistance Testing ◽  
Transmitted Drug Resistance ◽  
Acute Hiv Infection ◽  
Early Primary ◽  
The Cochrane Library

Abstract Background: In the absence of AIDS vaccine，antiretroviral therapy (ART) was the most effective tool to prevent and control the HIV pandemic. But the widespread use of ART has raised concerns about the emergence of HIV transmitted drug resistance (TDR). Acute HIV infection (AHI) was the most appropriate time to detect the spread of TDR. In this meta-analysis, our purpose was to evaluate the level of TDR in ART-naive patients with acute/ primary/ early HIV infection, and describe the critical drug-resistant mutations. Methods: We systematically reviewed 1192 studies published between January 1, 2008 and December 30, 2019 in PubMed, Web of Science, Embase, and the Cochrane Library, and selected 12 studies that meet our inclusion criteria. To evaluate the overall prevalence of TDR, we extracted raw data and analyzed prevalence estimates using Stata SE. Estimates of mixed-effects were calculated by random-effects meta-analysis, and the I²statistics were used to estimate the heterogeneity of all included studies.Results: The Data of this meta-analysis come from 12 observational studies, covering 3558 ART-naive individuals with PHI, AHI or EHI. The overall prevalence of HIV-TDR is 9.8% (95% confidence interval (CI): 7.2%–12.3%, p<0.001). Prevalence of resistance by drug class is highest for the NNRTIs at 5.9% (95% CI: 3.1%–8.6%, p<0.001), followed by NRTIs 3.4% (95% CI: 1.8%–5.0%, p<0.001) and PIs 3.4% (95% CI: 2.7%–4.0%, p<0.001). The prevalence of TDR to INIs is 0.3% (95% CI: -0.1%-0.7%, p<0.001), which is the lowest among all antiretroviral drugs.Conclusion: The overall prevalence of TDR is high among AHI patients who have never received ART. This emphasizes the importance of baseline drug resistance testing for public health surveillance and guiding the choice of ART. In addition, the prevalence of TDR to NNRTIs is the highest, while the TDR to INIs is the lowest. This may guide the selection of clinical antiretroviral drugs.

scholarly journals HIV-1 CRF63_02A6 models as a tool for evaluating efficacy of developing antiretroviral drugs

2020 ◽  
Vol 10 (4) ◽  
pp. 769-774
Author(s):  
D. P. Zyryanova ◽  
N. V. Bogacheva ◽  
A. V. Totmenin ◽  
N. M. Gashnikova
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Highly Active Antiretroviral Therapy ◽  
Federal District ◽  
Antiretroviral Drugs ◽  
Infection Process ◽  
Reverse Transcriptase Inhibitors ◽  
Infectious Molecular Clones ◽  
Hiv 1

Highly active antiretroviral therapy (HAART) allows not only to control the infection process in certain patient, but also to reduce a risk of HIV infection spreading in general, so that one of the goals for international community fighting against HIV-spread is to maximize coverage of infected subjects with HAART. Antiretroviral therapy in HIV infection is administered lifelong, so that therapeutic efficacy may be lowered due to emergence of resistant HIV-1 variants. Currently, development of new antiretroviral drugs is currently underway throughout the world, therefore standard HIV-1 models are demanded to evaluate antiviral efficacy of promising drugs. To reliably assess drug efficiency regarding Russiawide HIV-1 variants, HIV-1 genovariants widespread in Russia should be used as a virus model. A recently emerged recombinant form of CRF63_02A6 HIV-1 is spread in Russia being currently a dominant variant detected among HIV-infected individuals in an extended region of the Siberian Federal District: in the Novosibirsk, Tomsk, Omsk, Kemerovo Regions, Krasnoyarsk and Altai Krai. We have obtained CRF63_02A6 infectious isolates of HIV-1, one of which contains mutations, reducing the sensitivity to the applied inhibitors of the virus reverse transcriptase. In addition, we constructed infectious molecular clones based on HIV-1 CRF63_02A6 variants with an affinity for CCR5 coreceptors and CXCR4. Infectious isolates and molecular clones CRF63_02A6 tested as models for assessing efficacy of antiretroviral drugs using the example of the drug “Efavirenz”. The fifty percent inhibitory concentration determined on the models of HIV-1 infectious molecular clones and HIV-1 isolate 18RU7056 ranged from 0.00027 pg/ml to 0.00046 pg/ml being in agreement with data published elsewhere. Concentrations of “Efavirenz” used in the study did not suppress the replication of HIV-1 12RU6987, which is resistant to non-nucleoside reverse transcriptase inhibitors, which confirms the decrease in the sensitivity of HIV-1 12RU6987 to “Efavirenz” by no less than 10,000 times. Thus, our data demonstrate that CRF63_02A6 HIV-1 isolated strains and infectious molecular clones are relevant and complementary tools for assessing efficacy of developing drugs aimed at suppressing HIV-1, including non-nucleoside-resistant virus reverse transcriptase inhibitors.

An Overview of Antiretroviral Agents for Treating HIV Infection in Paediatric Population

2020 ◽  
Vol 27 (5) ◽  
pp. 760-794 ◽  
Author(s):  
Rita Melo ◽  
Agostinho Lemos ◽  
António J. Preto ◽  
Beatriz Bueschbell ◽  
Pedro Matos-Filipe ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Targeted Delivery ◽  
Highly Active Antiretroviral Therapy ◽  
Antiretroviral Drugs ◽  
Viral Reservoir ◽  
Reverse Transcriptase Inhibitors ◽  
Replication Process ◽  
Antiretroviral Agents ◽  
Multiple Drugs

Paediatric Acquired ImmunoDeficiency Syndrome (AIDS) is a life-threatening and infectious disease in which the Human Immunodeficiency Virus (HIV) is mainly transmitted through Mother-To- Child Transmission (MTCT) during pregnancy, labour and delivery, or breastfeeding. This review provides an overview of the distinct therapeutic alternatives to abolish the systemic viral replication in paediatric HIV-1 infection. Numerous classes of antiretroviral agents have emerged as therapeutic tools for downregulation of different steps in the HIV replication process. These classes encompass Non- Nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs), Nucleoside/Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs/NtRTIs), INtegrase Inhibitors (INIs), Protease Inhibitors (PIs), and Entry Inhibitors (EIs). Co-administration of certain antiretroviral drugs with Pharmacokinetic Enhancers (PEs) may boost the effectiveness of the primary therapeutic agent. The combination of multiple antiretroviral drug regimens (Highly Active AntiRetroviral Therapy - HAART) is currently the standard therapeutic approach for HIV infection. So far, the use of HAART offers the best opportunity for prolonged and maximal viral suppression, and preservation of the immune system upon HIV infection. Still, the frequent administration of high doses of multiple drugs, their inefficient ability to reach the viral reservoirs in adequate doses, the development of drug resistance, and the lack of patient compliance compromise the complete HIV elimination. The development of nanotechnology-based drug delivery systems may enable targeted delivery of antiretroviral agents to inaccessible viral reservoir sites at therapeutic concentrations. In addition, the application of Computer-Aided Drug Design (CADD) approaches has provided valuable tools for the development of anti-HIV drug candidates with favourable pharmacodynamics and pharmacokinetic properties.

Neuropsychiatric adverse effects of HIV antiviral medication

2017 ◽  
Vol 41 (S1) ◽  
pp. S697-S698
Author(s):  
S. Nascimento ◽  
M. Mendes ◽  
C. Solana ◽  
M. Croca ◽  
J. Reis
Keyword(s):  
Antiretroviral Therapy ◽  
Adverse Effects ◽  
Reverse Transcriptase ◽  
Opportunistic Infections ◽  
Antiretroviral Drugs ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Neuropsychiatric Complications ◽  
Competing Interest ◽  
Neuropsychiatric Adverse Effects

IntroductionHIV (human immunodeficiency virus) infection is related to several neuropsychiatric complications, such as dementia, encephalopathy, psychosis, as well as, opportunistic infections of the central nervous system (CNS). The discovery of antiretroviral therapy (ART) has limited these conditions and extended the life span of infected patients into a chronic illness, but it is also associated with neuropsychiatric adverse effects.ObjectivesTo review the literature on the most common neuropsychiatric complications of the ART, since it can be difficult to distinguish drugs toxicity, the effects of the virus, immune system and psycho-social events.MethodsThe authors have conducted an online search in PubMed with the terms: “Psychiatry”, “HIV”, “adverse effects” and “antiretroviral drugs” from 2011 until 2016. From the outcome were collected, analyzed and summarized the articles considered to be relevant.ResultsThe antiretroviral therapy (ART) are associated with a numerous adverse effects on the central and peripheral nervous systems, as well as, metabolic, gastrointestinal, cardiac, and other toxicities. The neuropsychiatric effects are common and highly variable, including depression, cognitive impairment and sleep disturbance. The nucleoside reverse transcriptase inhibitors and the non-nucleoside reverse transcriptase inhibitors are one of the two classes of antiviral drugs most frequently associated with neuropsychiatric complications.ConclusionsThe occurrence of new-onset conditions related to ART makes it difficult to determine the association between psychiatric disorders and ART adverse effects, and given the fact that patients commit to lifelong therapy, as well as, they can diminish quality of life; it makes these assessment important in treating these conditions.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Increase in HIV-1-transmitted drug resistance among ART-naïve youths at the China-Myanmar border during 2009 ~ 2017

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yibo Ding ◽  
Min Chen ◽  
Jibao Wang ◽  
Yuecheng Yang ◽  
Yi Feng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Cd4 Count ◽  
Transmitted Drug Resistance ◽  
Subtype C ◽  
Reverse Transcriptase Inhibitors ◽  
Recombination Hotspots ◽  
Subtype B ◽  
Sex With Men ◽  
Hiv 1

Abstract Background HIV-transmitted drug resistance (TDR) is found in antiretroviral therapy (ART)-naïve populations infected with HIV-1 with TDR mutations and is important for guiding future first- and second-line ART regimens. We investigated TDR and its effect on CD4 count in ART-naïve youths from the China-Myanmar border near the Golden Triangle to better understand TDR and effectively guide ART. Methods From 2009 to 2017, 10,832 HIV-1 infected individuals were newly reported along the Dehong border of China, 573 ART-naïve youths (16 ~ 25 y) were enrolled. CD4 counts were obtained from whole blood samples. HIV pol gene sequences were amplified from RNA extracted from plasma. The Stanford REGA program and jpHMM recombination prediction tool were used to determine genotypes. TDR mutations (TDRMs) were analyzed using the Stanford Calibrated Population Resistance tool. Results The most common infection route was heterosexuals (70.51%), followed by people who inject drugs (PWID, 19.20%) and men who have sex with men (MSM) (8.90%). The distribution of HIV genotypes mainly included the unique recombinant form (URF) (44.08%), 38.68% were CRFs, 13.24% were subtype C and 4.04% were subtype B. The prevalence of TDR increased significantly from 2009 to 2017 (3.48 to 9.48%) in ART-naïve youths (4.00 to 13.16% in Burmese subjects, 3.33 to 5.93% in Chinese subjects), and the resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 3.49, 2.62, and 0.52%, respectively. Most (94.40%, n = 34) of HIV-1-infected patients with TDRM had mutation that conferred resistance to a single drug class. The most common mutations Y181I/C and K103N, were found in 7 and 9 youths, respectively. The mean CD4 count was significantly lower among individuals with TDRMs (373/mm3 vs. 496/mm3, p = 0.013). Conclusions The increase in the prevalence of HIV-1 TDR increase and a low CD4 count of patients with TDRMs in the China-Myanmar border suggests the need for considering drug resistance before initiating ART in HIV recombination hotspots.

PREVALENCE AND STRUCTURE OF HIV-1 DRUG RESISTANCE AMONG TREATMENT NAÏVE PATIENTS SINCE THE INTRODUCTION OF ANTIRETROVIRAL THERAPY IN THE RUSSIAN FEDERATION

2019 ◽  
Vol 11 (2) ◽  
pp. 75-83 ◽  
Author(s):  
A. A. Kirichenko ◽  
D. E. Kireev ◽  
A. E. Lopatukhin ◽  
A. V. Murzakova ◽  
I. A. Lapovok ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Russian Federation ◽  
Antiretroviral Drugs ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Treatment Naïve ◽  
The Russian Federation ◽  
Hiv 1

Aim: to analyze the prevalence, structure of drug resistance and drug resistance mutations in the protease and reverse transcriptase genes of HIV-1 among treatment naïve patients.Materials and methods. We analyzed protease and reverse transcriptase sequences from 1560 treatment naïve HIV-infected patients from all Federal Districts of the Russian Federation with the first positive immune blot during 1998–2017. Sequences were analyzed for the presence of drug resistance mutations and predicted drug resistance to antiretroviral drugs using two algorithms — Stanford HIVDR Database (HIVdb) and the 2009 SDRM list (CPR).Results. The prevalence of drug resistance mutations was 11,1%. More often the prevalence of drug resistance was found for non-nucleoside reverse transcriptase inhibitor drugs (rilpivirine, nevirapine, efavirenz). The prevalence of transmitted drug resistance associated with mutations from the SDRM list was 5,3%, which is classified by the WHO as a moderate level. However, it should be noted that since the large-scale use of antiretroviral drugs in the Russian Federation, there has been a trend towards a gradual increase in the level of the transmitted drug resistance, and in 2016 it has already reached 6,1%.Conclusion. The results demonstrate the need for regular surveillance of the prevalence of HIV drug resistance to antiretroviral drugs among treatment naïve patients in the Russian Federation.

scholarly journals Increasing Prevalence of HIV-1 Transmitted Drug Resistance in Portugal: Implications for First Line Treatment Recommendations

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1238
Author(s):  
Marta Pingarilho ◽  
Victor Pimentel ◽  
Isabel Diogo ◽  
Sandra Fernandes ◽  
Mafalda Miranda ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Transmitted Drug Resistance ◽  
Reverse Transcriptase Inhibitors ◽  
Genotypic Resistance ◽  
Acquired Drug Resistance ◽  
Subtype B ◽  
Number Of Patients

Introduction: Treatment for All recommendations have allowed access to antiretroviral (ARV) treatment for an increasing number of patients. This minimizes the transmission of infection but can potentiate the risk of transmitted (TDR) and acquired drug resistance (ADR). Objective: To study the trends of TDR and ADR in patients followed up in Portuguese hospitals between 2001 and 2017. Methods: In total, 11,911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutation according to the WHO surveillance list. Genotypic resistance to ARV was evaluated with Stanford HIVdb v7.0. Patterns of TDR, ADR and the prevalence of mutations over time were analyzed using logistic regression. Results and Discussion: The prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (p < 0.001). This was due to a significant increase in both resistance to nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs), from 5.6% to 6.7% (p = 0.002) and 2.9% to 8.9% (p < 0.001), respectively. TDR was associated with infection with subtype B, and with lower viral load levels (p < 0.05). The prevalence of ADR declined from 86.6% in 2001 to 51.0% in 2017 (p < 0.001), caused by decreasing drug resistance to all antiretroviral (ARV) classes (p < 0.001). Conclusions: While ADR has been decreasing since 2001, TDR has been increasing, reaching a value of 13.1% by the end of 2017. It is urgently necessary to develop public health programs to monitor the levels and patterns of TDR in newly diagnosed patients.

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